More on Science
Michael Hunter, MD
2 years ago
5 Drugs That May Increase Your Risk of Dementia
While our genes can't be changed easily, you can avoid some dementia risk factors. Today we discuss dementia and five drugs that may increase risk.
Memory loss appears to come with age, but we're not talking about forgetfulness. Sometimes losing your car keys isn't an indication of dementia. Dementia impairs the capacity to think, remember, or make judgments. Dementia hinders daily tasks.
Alzheimers is the most common dementia. Dementia is not normal aging, unlike forgetfulness. Aging increases the risk of Alzheimer's and other dementias. A family history of the illness increases your risk, according to the Mayo Clinic (USA).
Given that our genes are difficult to change (I won't get into epigenetics), what are some avoidable dementia risk factors? Certain drugs may cause cognitive deterioration.
Today we look at four drugs that may cause cognitive decline.
Dementia and benzodiazepines
Benzodiazepine sedatives increase brain GABA levels. Example benzodiazepines:
Diazepam (Valium) (Valium)
Alprazolam (Xanax) (Xanax)
Clonazepam (Klonopin) (Klonopin)
Addiction and overdose are benzodiazepine risks. Yes! These medications don't raise dementia risk.
USC study: Benzodiazepines don't increase dementia risk in older adults.
Benzodiazepines can produce short- and long-term amnesia. This memory loss hinders memory formation. Extreme cases can permanently impair learning and memory. Anterograde amnesia is uncommon.
2. Statins and dementia
Statins reduce cholesterol. They prevent a cholesterol-making chemical. Examples:
Atorvastatin (Lipitor) (Lipitor)
Fluvastatin (Lescol XL) (Lescol XL)
Lovastatin (Altoprev) (Altoprev)
Pitavastatin (Livalo, Zypitamag) (Livalo, Zypitamag)
Pravastatin (Pravachol) (Pravachol)
Rosuvastatin (Crestor, Ezallor) (Crestor, Ezallor)
Simvastatin (Zocor) (Zocor)
This finding is contentious. Harvard's Brigham and Womens Hospital's Dr. Joann Manson says:
“I think that the relationship between statins and cognitive function remains controversial. There’s still not a clear conclusion whether they help to prevent dementia or Alzheimer’s disease, have neutral effects, or increase risk.”
This one's off the dementia list.
3. Dementia and anticholinergic drugs
Anticholinergic drugs treat many conditions, including urine incontinence. Drugs inhibit acetylcholine (a brain chemical that helps send messages between cells). Acetylcholine blockers cause drowsiness, disorientation, and memory loss.
First-generation antihistamines, tricyclic antidepressants, and overactive bladder antimuscarinics are common anticholinergics among the elderly.
Anticholinergic drugs may cause dementia. One study found that taking anticholinergics for three years or more increased the risk of dementia by 1.54 times compared to three months or less. After stopping the medicine, the danger may continue.
4. Drugs for Parkinson's disease and dementia
Cleveland Clinic (USA) on Parkinson's:
Parkinson's disease causes age-related brain degeneration. It causes delayed movements, tremors, and balance issues. Some are inherited, but most are unknown. There are various treatment options, but no cure.
Parkinson's medications can cause memory loss, confusion, delusions, and obsessive behaviors. The drug's effects on dopamine cause these issues.
A 2019 JAMA Internal Medicine study found powerful anticholinergic medications enhance dementia risk.
Those who took anticholinergics had a 1.5 times higher chance of dementia. Individuals taking antidepressants, antipsychotic drugs, anti-Parkinson’s drugs, overactive bladder drugs, and anti-epileptic drugs had the greatest risk of dementia.
Anticholinergic medicines can lessen Parkinson's-related tremors, but they slow cognitive ability. Anticholinergics can cause disorientation and hallucinations in those over 70.
5. Antiepileptic drugs and dementia
The risk of dementia from anti-seizure drugs varies with drugs. Levetiracetam (Keppra) improves Alzheimer's cognition.
One study linked different anti-seizure medications to dementia. Anti-epileptic medicines increased the risk of Alzheimer's disease by 1.15 times in the Finnish sample and 1.3 times in the German population. Depakote, Topamax are drugs.
Adam Frank
3 years ago
Humanity is not even a Type 1 civilization. What might a Type 3 be capable of?
The Kardashev scale grades civilizations from Type 1 to Type 3 based on energy harvesting.
How do technologically proficient civilizations emerge across timescales measuring in the tens of thousands or even millions of years? This is a question that worries me as a researcher in the search for “technosignatures” from other civilizations on other worlds. Since it is already established that longer-lived civilizations are the ones we are most likely to detect, knowing something about their prospective evolutionary trajectories could be translated into improved search tactics. But even more than knowing what to seek for, what I really want to know is what happens to a society after so long time. What are they capable of? What do they become?
This was the question Russian SETI pioneer Nikolai Kardashev asked himself back in 1964. His answer was the now-famous “Kardashev Scale.” Kardashev was the first, although not the last, scientist to try and define the processes (or stages) of the evolution of civilizations. Today, I want to launch a series on this question. It is crucial to technosignature studies (of which our NASA team is hard at work), and it is also important for comprehending what might lay ahead for mankind if we manage to get through the bottlenecks we have now.
The Kardashev scale
Kardashev’s question can be expressed another way. What milestones in a civilization’s advancement up the ladder of technical complexity will be universal? The main notion here is that all (or at least most) civilizations will pass through some kind of definable stages as they progress, and some of these steps might be mirrored in how we could identify them. But, while Kardashev’s major focus was identifying signals from exo-civilizations, his scale gave us a clear way to think about their evolution.
The classification scheme Kardashev employed was not based on social systems of ethics because they are something that we can probably never predict about alien cultures. Instead, it was built on energy, which is something near and dear to the heart of everybody trained in physics. Energy use might offer the basis for universal stages of civilisation progression because you cannot do the work of establishing a civilization without consuming energy. So, Kardashev looked at what energy sources were accessible to civilizations as they evolved technologically and used those to build his scale.
From Kardashev’s perspective, there are three primary levels or “types” of advancement in terms of harvesting energy through which a civilization should progress.
Type 1: Civilizations that can capture all the energy resources of their native planet constitute the first stage. This would imply capturing all the light energy that falls on a world from its host star. This makes it reasonable, given solar energy will be the largest source available on most planets where life could form. For example, Earth absorbs hundreds of atomic bombs’ worth of energy from the Sun every second. That is a rather formidable energy source, and a Type 1 race would have all this power at their disposal for civilization construction.
Type 2: These civilizations can extract the whole energy resources of their home star. Nobel Prize-winning scientist Freeman Dyson famously anticipated Kardashev’s thinking on this when he imagined an advanced civilization erecting a large sphere around its star. This “Dyson Sphere” would be a machine the size of the complete solar system for gathering stellar photons and their energy.
Type 3: These super-civilizations could use all the energy produced by all the stars in their home galaxy. A normal galaxy has a few hundred billion stars, so that is a whole lot of energy. One way this may be done is if the civilization covered every star in their galaxy with Dyson spheres, but there could also be more inventive approaches.
Implications of the Kardashev scale
Climbing from Type 1 upward, we travel from the imaginable to the god-like. For example, it is not hard to envisage utilizing lots of big satellites in space to gather solar energy and then beaming that energy down to Earth via microwaves. That would get us to a Type 1 civilization. But creating a Dyson sphere would require chewing up whole planets. How long until we obtain that level of power? How would we have to change to get there? And once we get to Type 3 civilizations, we are virtually thinking about gods with the potential to engineer the entire cosmos.
For me, this is part of the point of the Kardashev scale. Its application for thinking about identifying technosignatures is crucial, but even more strong is its capacity to help us shape our imaginations. The mind might become blank staring across hundreds or thousands of millennia, and so we need tools and guides to focus our attention. That may be the only way to see what life might become — what we might become — once it arises to start out beyond the boundaries of space and time and potential.
This is a summary. Read the full article here.
Bob Service
3 years ago
Did volcanic 'glasses' play a role in igniting early life?
Quenched lava may have aided in the formation of long RNA strands required by primitive life.
It took a long time for life to emerge. Microbes were present 3.7 billion years ago, just a few hundred million years after the 4.5-billion-year-old Earth had cooled enough to sustain biochemistry, according to fossils, and many scientists believe RNA was the genetic material for these first species. RNA, while not as complicated as DNA, would be difficult to forge into the lengthy strands required to transmit genetic information, raising the question of how it may have originated spontaneously.
Researchers may now have a solution. They demonstrate how basaltic glasses assist individual RNA letters, also known as nucleoside triphosphates, join into strands up to 200 letters long in lab studies. The glasses are formed when lava is quenched in air or water, or when melted rock generated by asteroid strikes cools rapidly, and they would have been plentiful in the early Earth's fire and brimstone.
The outcome has caused a schism among top origin-of-life scholars. "This appears to be a great story that finally explains how nucleoside triphosphates react with each other to create RNA strands," says Thomas Carell, a scientist at Munich's Ludwig Maximilians University. However, Harvard University's Jack Szostak, an RNA expert, says he won't believe the results until the study team thoroughly describes the RNA strands.
Researchers interested in the origins of life like the idea of a primordial "RNA universe" since the molecule can perform two different functions that are essential for life. It's made up of four chemical letters, just like DNA, and can carry genetic information. RNA, like proteins, can catalyze chemical reactions that are necessary for life.
However, RNA can cause headaches. No one has yet discovered a set of plausible primordial conditions that would cause hundreds of RNA letters—each of which is a complicated molecule—to join together into strands long enough to support the intricate chemistry required to kick-start evolution.
Basaltic glasses may have played a role, according to Stephen Mojzsis, a geologist at the University of Colorado, Boulder. They're high in metals like magnesium and iron, which help to trigger a variety of chemical reactions. "Basaltic glass was omnipresent on Earth at the time," he adds.
He provided the Foundation for Applied Molecular Evolution samples of five different basalt glasses. Each sample was ground into a fine powder, sanitized, and combined with a solution of nucleoside triphosphates by molecular biologist Elisa Biondi and her colleagues. The RNA letters were unable to link up without the presence of glass powder. However, when the molecules were mixed with the glass particles, they formed long strands of hundreds of letters, according to the researchers, who published their findings in Astrobiology this week. There was no need for heat or light. Biondi explains, "All we had to do was wait." After only a day, little RNA strands produced, yet the strands continued to grow for months. Jan Paek, a molecular biologist at Firebird Biomolecular Sciences, says, "The beauty of this approach is its simplicity." "Mix the components together, wait a few days, and look for RNA."
Nonetheless, the findings pose a slew of problems. One of the questions is how nucleoside triphosphates came to be in the first place. Recent study by Biondi's colleague Steven Benner suggests that the same basaltic glasses may have aided in the creation and stabilization of individual RNA letters.
The form of the lengthy RNA strands, according to Szostak, is a significant challenge. Enzymes in modern cells ensure that most RNAs form long linear chains. RNA letters, on the other hand, can bind in complicated branching sequences. Szostak wants the researchers to reveal what kind of RNA was produced by the basaltic glasses. "It irritates me that the authors made an intriguing initial finding but then chose to follow the hype rather than the research," Szostak says.
Biondi acknowledges that her team's experiment almost probably results in some RNA branching. She does acknowledge, however, that some branched RNAs are seen in species today, and that analogous structures may have existed before the origin of life. Other studies carried out by the study also confirmed the presence of lengthy strands with connections, indicating that they are most likely linear. "It's a healthy argument," says Dieter Braun, a Ludwig Maximilian University origin-of-life chemist. "It will set off the next series of tests."
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Daniel Vassallo
3 years ago
Why I quit a $500K job at Amazon to work for myself
I quit my 8-year Amazon job last week. I wasn't motivated to do another year despite promotions, pay, recognition, and praise.
In AWS, I built developer tools. I could have worked in that field forever.
I became an Amazon developer. Within 3.5 years, I was promoted twice to senior engineer and would have been promoted to principal engineer if I stayed. The company said I had great potential.
Over time, I became a reputed expert and leader within the company. I was respected.
First year I made $75K, last year $511K. If I stayed another two years, I could have made $1M.
Despite Amazon's reputation, my work–life balance was good. I no longer needed to prove myself and could do everything in 40 hours a week. My team worked from home once a week, and I rarely opened my laptop nights or weekends.
My coworkers were great. I had three generous, empathetic managers. I’m very grateful to everyone I worked with.
Everything was going well and getting better. My motivation to go to work each morning was declining despite my career and income growth.
Another promotion, pay raise, or big project wouldn't have boosted my motivation. Motivation was also waning. It was my freedom.
Demotivation
My motivation was high in the beginning. I worked with someone on an internal tool with little scrutiny. I had more freedom to choose how and what to work on than in recent years. Me and another person improved it, talked to users, released updates, and tested it. Whatever we wanted, we did. We did our best and were mostly self-directed.
In recent years, things have changed. My department's most important project had many stakeholders and complex goals. What I could do depended on my ability to convince others it was the best way to achieve our goals.
Amazon was always someone else's terms. The terms started out simple (keep fixing it), but became more complex over time (maximize all goals; satisfy all stakeholders). Working in a large organization imposed restrictions on how to do the work, what to do, what goals to set, and what business to pursue. This situation forced me to do things I didn't want to do.
Finding New Motivation
What would I do forever? Not something I did until I reached a milestone (an exit), but something I'd do until I'm 80. What could I do for the next 45 years that would make me excited to wake up and pay my bills? Is that too unambitious? Nope. Because I'm motivated by two things.
One is an external carrot or stick. I'm not forced to file my taxes every April, but I do because I don't want to go to jail. Or I may not like something but do it anyway because I need to pay the bills or want a nice car. Extrinsic motivation
One is internal. When there's no carrot or stick, this motivates me. This fuels hobbies. I wanted a job that was intrinsically motivated.
Is this too low-key? Extrinsic motivation isn't sustainable. Getting promoted felt good for a week, then it was over. When I hit $100K, I admired my W2 for a few days, but then it wore off. Same thing happened at $200K, $300K, $400K, and $500K. Earning $1M or $10M wouldn't change anything. I feel the same about every material reward or possession. Getting them feels good at first, but quickly fades.
Things I've done since I was a kid, when no one forced me to, don't wear off. Coding, selling my creations, charting my own path, and being honest. Why not always use my strengths and motivation? I'm lucky to live in a time when I can work independently in my field without large investments. So that’s what I’m doing.
What’s Next?
I'm going all-in on independence and will make a living from scratch. I won't do only what I like, but on my terms. My goal is to cover my family's expenses before my savings run out while doing something I enjoy. What more could I want from my work?
You can now follow me on Twitter as I continue to document my journey.
This post is a summary. Read full article here
Jano le Roux
3 years ago
The Real Reason Adobe Just Paid $20 billion for Figma
Sketch or Figma?
Designers are pissed.
The beast ate the beauty.
Figma deserves $20B.
Do designers deserve Adobe?
Adobe devours new creative tools and spits them out with a slimy Adobe aftertaste.
Frame.io — $1.3B
Magento — $1.7B
Macromedia — $3.6B
Nothing compares to the risky $20B acquisition.
If they can't be beaten, buy them.
And then make them boring.
Adobe's everywhere.
Like that friend who dabbles in everything creatively, there's not enough time to master one thing.
Figma was Adobe's thigh-mounted battle axe.
a UX design instrument with a sizable free tier.
a UX design tool with a simple and quick user interface.
a tool for fluid collaboration in user experience design.
a web-based UX design tool that functions well.
a UX design tool with a singular goal of perfection.
UX design software that replaced Adobe XD.
Adobe XD could do many of Figma's things, but it didn't focus on the details. This is a major issue when working with detail-oriented professionals.
UX designers.
Design enthusiasts first used Figma. More professionals used it. Institutions taught it. Finally, major brands adopted Figma.
Adobe hated that.
Adobe dispatched a team of lawyers to resolve the Figma issue, as big companies do. Figma didn’t bite for months.
Oh no.
Figma resisted.
Figma helped designers leave Adobe. Figma couldn't replace Photoshop, but most designers used it to remove backgrounds.
Online background removal tools improved.
The Figma problem grew into a thorn, a knife, and a battle ax in Adobe's soft inner thigh.
Figma appeared to be going public. Adobe couldn’t allow that. It bought Figma for $20B during the IPO drought.
Adobe has a new issue—investors are upset.
The actual cause of investors' ire toward Adobe
Spoiler: The math just doesn’t add up.
According to Adobe's press release, Figma's annual recurring revenue (ARR) is $400M and growing rapidly.
The $20B valuation requires a 50X revenue multiple, which is unheard of.
Venture capitalists typically use:
10% to 29% growth per year: ARR multiplied by 1 to 5
30% to 99% growth per year: ARR multiplied by 6 to 10
100% to 400% growth per year: ARR multiplied by 10 to 20
Showing an investor a 50x multiple is like telling friends you saw a UFO. They'll think you're crazy.
Adobe's stock fell immediately after the acquisition because it didn't make sense to a number-cruncher.
Designers started a Tweet storm in the digital town hall where VCs and designers often meet.
Adobe acquired Workfront for $1.5 billion at the end of 2020. This purchase made sense for investors.
Many investors missed the fact that Adobe is acquiring Figma not only for its ARR but also for its brilliant collaboration tech.
Adobe could use Figmas web app technology to make more products web-based to compete with Canva.
Figma's high-profile clients could switch to Adobe's enterprise software.
However, questions arise:
Will Adobe make Figma boring?
Will Adobe tone down Figma to boost XD?
Would you ditch Adobe and Figma for Sketch?
Thomas Tcheudjio
3 years ago
If you don't crush these 3 metrics, skip the Series A.
I recently wrote about getting VCs excited about Marketplace start-ups. SaaS founders became envious!
Understanding how people wire tens of millions is the only Series A hack I recommend.
Few people understand the intellectual process behind investing.
VC is risk management.
Series A-focused VCs must cover two risks.
1. Market risk
You need a large market to cross a threshold beyond which you can build defensibilities. Series A VCs underwrite market risk.
They must see you have reached product-market fit (PMF) in a large total addressable market (TAM).
2. Execution risk
When evaluating your growth engine's blitzscaling ability, execution risk arises.
When investors remove operational uncertainty, they profit.
Series A VCs like businesses with derisked revenue streams. Don't raise unless you have a predictable model, pipeline, and growth.
Please beat these 3 metrics before Series A:
Achieve $1.5m ARR in 12-24 months (Market risk)
Above 100% Net Dollar Retention. (Market danger)
Lead Velocity Rate supporting $10m ARR in 2–4 years (Execution risk)
Hit the 3 and you'll raise $10M in 4 months. Discussing 2/3 may take 6–7 months.
If none, don't bother raising and focus on becoming a capital-efficient business (Topics for other posts).
Let's examine these 3 metrics for the brave ones.
1. Lead Velocity Rate supporting €$10m ARR in 2 to 4 years
Last because it's the least discussed. LVR is the most reliable data when evaluating a growth engine, in my opinion.
SaaS allows you to see the future.
Monthly Sales and Sales Pipelines, two predictive KPIs, have poor data quality. Both are lagging indicators, and minor changes can cause huge modeling differences.
Analysts and Associates will trash your forecasts if they're based only on Monthly Sales and Sales Pipeline.
LVR, defined as month-over-month growth in qualified leads, is rock-solid. There's no lag. You can See The Future if you use Qualified Leads and a consistent formula and process to qualify them.
With this metric in your hand, scaling your company turns into an execution play on which VCs are able to perform calculations risk.
2. Above-100% Net Dollar Retention.
Net Dollar Retention is a better-known SaaS health metric than LVR.
Net Dollar Retention measures a SaaS company's ability to retain and upsell customers. Ask what $1 of net new customer spend will be worth in years n+1, n+2, etc.
Depending on the business model, SaaS businesses can increase their share of customers' wallets by increasing users, selling them more products in SaaS-enabled marketplaces, other add-ons, and renewing them at higher price tiers.
If a SaaS company's annualized Net Dollar Retention is less than 75%, there's a problem with the business.
Slack's ARR chart (below) shows how powerful Net Retention is. Layer chart shows how existing customer revenue grows. Slack's S1 shows 171% Net Dollar Retention for 2017–2019.
Slack S-1
3. $1.5m ARR in the last 12-24 months.
According to Point 9, $0.5m-4m in ARR is needed to raise a $5–12m Series A round.
Target at least what you raised in Pre-Seed/Seed. If you've raised $1.5m since launch, don't raise before $1.5m ARR.
Capital efficiency has returned since Covid19. After raising $2m since inception, it's harder to raise $1m in ARR.
P9's 2016-2021 SaaS Funding Napkin
In summary, less than 1% of companies VCs meet get funded. These metrics can help you win.
If there’s demand for it, I’ll do one on direct-to-consumer.
Cheers!